Early detection of esophageal adenocarcinoma is a significant diagnostic challenge and current surveillance methods are problematic and limited. Advanced endoscopic imaging tools are a currently active area of research and show promise for improving surveillance for early detection of dysplasia. Microendoscopy is a real-time optical biopsy imaging method which can be deployed at the time of endoscopy and can observe microscopic architectural features of dysplastic epithelium. These systems have great potential to not only improve detection rates, but have been limited to observations of structural changes in tissue only. There are also significant functional changes in the microenvironment of dysplastic epithelium that are associated with cellular growth beyond the oxygen and glucose diffusion limits. Specifically, how these cells adapt metabolically to such changes during the course of tumor progression has important implications for their survival. We have developed a hybrid microendoscope probe based on high-resolution and diffuse reflectance imaging and spectroscopy, which will be sensitive to these functional changes which occur during tumorigenesis. The goal of this project is to use advanced optical imaging techniques to identify the key microendoscopically-measureable functional or metabolic biomarkers associated with tumor progression and to validate our microendoscopy approach on optical phantoms and murine gastrointestinal epithelial tissue. We will employ a transgenic murine model of gastrointenstinal dysplasia in a cross-sectional study of cancer progression as well as murine tumor xenografts to systematically observe and quantify these key biomarkers of dysplasia progression and response to therapeutic interventions. At the conclusion of this study, we will have validated our hybrid microendoscopy device and developed a toolbox of optical biomarkers which will enhance early detection of gastrointestinal dysplasia and effectively guide future therapeutic interventions in patients with newly diagnosed gastrointestinal cancers.